Synthesis of adamantane derivatives



United States Patent Ofiice 3,335,193

Patented Aug. 8, 1 967 of 1-2 carbon atoms, and each R is hydrogen or alkyl 3,335,193 of 1-2 carbon atoms. The adamantane product thereby SYNTHESIS OF ADAMANTANE DERIVATIVES obtained has the formula George A. Olah, Wellesley, Mass., assignor to The Dow Chemical Company, Midland, Mich., a corporation of i z ii 1 9 s 1 6 5 C 0 rawing. Fi ed Dec. 28, 1 64, er. No. 42 70 6 Claims. c1. 260--648) E CHR I o-oHR The present invention relates to a new chemical process, or more particularly, to an improvement which ex- 10 i R tends the utility of a known process. CHR C R It has been disccovered recently (see Schleyer et al.,

I. Am. Chem. Soc., 82, 4645 (1960)) that tetrahydrodicyclopentadiene (hexahydro-4,7-methanoindane) and its lower alkyl derivatives are converted to the corresponding adamantanes when contacted with an aluminum halide catalyst at moderate temperatures. This method offers a route to hitherto scarce compounds containing the adamantane nucleus. However, some substituted adamantanes are not obtainable by this process. For example, halotetrahydrodicyclopentadienes which would be expected to give the adamantyl halides on rearrangement are found to yield no such product when treated with aluminum chloride in the usual way. These adamantyl halides are valuable intermediates for making 1-adamantol, l-adamantylamine, and other derivatives having antimicrobial and other similar biological properties which previously have had to be prepared by less direct means with consequent loss of efiiciency and convenience. Representative of such derivatives are l-adamantyl substituted amines and l'adamantyloxy or l'adamantylthio to 150 C. Higher temperatures cause excessive decomderivatives of penicillin.

. position and side reactions. The process 18 usually best It has now been found that such l-adamantyl halides Operated at Reaction times of 0'1 10 hours can be prepared successfully by rearrangement when an aluminum halide is employed as a complex with a nitro lower alkane. This aluminum halide-nitroalkane complex has a specific activity different from that of the unmodified halide. The rearrangement of the substituted tetrahydrodicyclopentadiene proceeds smoothly under moderate reaction conditions to give good yields of the corresponding l-adamantyl derivative. The catalyst complex is represented by the formula where X and Y are attached in the l and 3 positions on bridgehead carbon atoms as shown.

The halogenated tetrahydrodicyclopentadiene starting materials whose general formula appears above are easily made from the readily available dicyclopentadiene or its alkyl substituted derivatives by adding a molecule of hydrogen halide or of halogen to one double bond in the dicyclopentadiene molecule and hydrogenating the other double bond by conventional methods.

The quantity of aluminum halide employed in the reaction can be any quantity conventionally used in alumi num halide-catalyzed rearrangements. While that quantity can vary from about 0.5% by weight of the starting compound to an equal weight or even more, the proportion of aluminum halide is preferably about 5-25 by weight.

The rearrangement proceeds satisfactorily at moderate temperatures within the approximate range of 50 C.

are ordinarily sufiicient to obtain optimum results.

The separation of the substituted adamantane product from the reaction mixture offers no unusual problems. After removal of the aluminum halide catalyst and, preferably, at least some of the nitroalkane, for example, by 40 water washing and evaporation or distillation, the ada mantane product can be separated from the remainder of the reaction mixture by conventional means such as extraction or distillation under reduced pressure. A partic- AlX -C H NO ularly eifective means is fractional crystillization. where X is halogen, usually chlorine or bromine, and n Example 1 is 1-4. Although this formula shows a 1:1 molecular 1k b d bl A solution of 0.5 g. of aluminum chloride in 20 ml. of Combmanon mtroa am est 11.86 m cons 2 nitromethane was added to 5 g. of 5-chloro-3a, 4,5,6,7,7aexcess so that it serves as t e reaction solvent. Mrxe heXahYdroA,7 methanoindane in 40 mL of nitromethane nitroeilkimes Of the formula 29 a be used h 1 5 producing an orange-yellow solution. This solution was Thls Improved Process 15 e ec we m rearrangmg a heated at reflux temperature for one hour, then cooled,

genated tetrahydrodicyclopentadienes of the formula washed free of acid with watfir and dried. The organic R chloride present was found to consist of 31% of l-chlorol adamantane and 69% unchanged starting material. The

solvent was distilled from the solution and the l-chloro- YCH CCHR adamantane was isolated by crystallrzing it from the residue. P03 ExampleZ G R CHR By the procedure of Example 1, l-bromoadamantane was obtained in similar yield by refluxing a solution of 5 -bromo-3a,4,5,6,7,7a-hexahydro 4,7 methanoindane in wherein X is halogen, Y is hydrogen, halogen, or alkyl nitromethane containing about 1% of anhydrous alumi- 3 num bromide based on the weight of the starting substituted indane.

Example 3 In the same way, 1-chloro-3-methyladamantane was prepared by heating at reflux temperature a solution of 5-chloro-6-methyl-3a,4,5,6,7,7a-hexahydro-4,7 methanoindane in nitromethane containing a little aluminum chloride.

In the manner illustrated by the above examples, 5,6- dibromohexahydro-4,7-methanoindane is heated with a catalytic quantity of aluminum bromide in nitroethane solution to produce 1,3 dibromoadamantane, 5 fluorohexahydro-4,7-methanoindane is reacted in nitropropane solution with aluminum chloride to give l-fiuoroadamantane, S-iodohexahydro-4,7-methanoindane and aluminum iodide are stirred in nitromethane solution to form 1- iodoadamantane, and 5 bromo 6-chloroheXahydro-4,7- methanoindane (from the addition of a mole of BrCl to dicyclopentadiene and hydrogenation of the product) is reacted with aluminum chloride in nitromethane solution to obtain 1-chloro-3-bromoadamantane.

I claim:

1. A process for making a l-adamantyl halide which comprises reacting by contacting at about 50 C. to about 150 C. an efiective amount of an aluminum halide in a nitro lower alkane with a compound of the formula wherein X ishalogen, Y is selected from the group consisting of hydrogen, halogen, and alkyl of 12 carbon atoms, and each R is selected from the group consisting of hydrogen and alkyl of 1-2 carbon atoms.

2. The process of claim 1 wherein each R ishydrogen, X is halogen, and Y is hydrogen.

3. The process of claim 2 wherein X is chlorine.

4. The process of claim 2 wherein X is bromine.

5. The process of claim 1 wherein X is halogen and Y is alkyl of 1-2 carbon atoms;

6. The process of claim 5 wherein X is chlorine and Y is methyl.

References Cited Olah: Friedel Crafts and Related Reactions, pages 246 and 299 (1963).

LEON ZITVER, Primary Examiner.

M. M. JACOB, Assistant Examiner. 

1. A PROCESS FOR MAKING A 1-ADAMANTYL-HALIDE WHICH COMPRISES REACTING BY CONTACTING AT ABOUT -50*C. TO ABOUT 150*C. AN EFFECTIVE AMOUNT OF AN ALUMINUM HALIDE IN A NITRO LOWER ALKANE WITH A COMPOUND OF THE FORMULA 